From investigational product to active reference: evolution of oral sumatriptan efficacy versus placebo for the treatment of acute migraine episodes and potential impact in comparative analyses

ABSTRACT Background: The relative efficacy and safety can vary among drugs over time. Sumatriptan, a first choice drug for acute migraine, can illustrate this phenomenon. Objective: To assess the evolution of the relative efficacy and tolerability of oral sumatriptan against placebo between its approval in 1991 and 2006. Methods: A systematic literature review of randomized controlled trials (RCTs) of adults suffering from acute migraine episodes was performed using Medline. Meta-analyses estimated odds ratios of the occurrence of pain-free at 2 hours and of any adverse event. Results: Out of the 67 RCTs identi.fied, pain-free at 2 hours and adverse events were reported in 25 and 28 studies, respectively. For pain-free, the relative effect of sumatriptan increases considerably over time, despite an increase in the absolute placebo effect. The odds ratio (95% CI) equaled 3.13 (1.67–5.86) around approval (1991–1994) and increased up to 4.14 (3.67–4.67) on the following decade. No specific variation was observed in the relative tolerability effect of sumatriptan over placebo over time. Conclusions: The relative effect of sumatriptan evolved substantially over time. This phenomenon may impact the results of network meta-analysis and indirect comparisons performed to evaluate the potential of a new drug, compared to widely prescribed older drugs